Individual and Combined Effects of Dietary Factors on Risk of Incident Hypertension: Prospective Analysis From the NutriNet-Santé Cohort.
Dietary intake is pointed as one of the major determinants in hypertension development. Data in the area are mostly obtained from cross-sectional studies. We aimed to investigate the prospective association between (1) individual nutritional factors and (2) adherence to the Dietary Approach to Stop Hypertension and the risk of incident hypertension in a large cohort study. We prospectively examined the incidence of hypertension among 80 426 French adults participating in the NutriNet-Santé cohort study. Self-reported sociodemographic, lifestyle health questionnaires and dietary consumption assessed by three 24-hour records were completed at baseline and yearly thereafter. Associations between quartiles (Q) of nutrients and food groups and adherence to Dietary Approach to Stop Hypertension diet and hypertension risk were assessed by multivariable Cox proportional hazards models. During a mean follow-up of 3.4±2.1 years, 2413 cases of incident hypertension were documented. Dietary intakes of sodium (Q4 versus Q1): hazard ratio (HR)=1.17 (95% confidence interval [CI], 1.02-1.35), potassium: HR=0.82 (95% CI, 0.72-0.94), animal protein: HR=1.26 (95% CI, 1.11-1.43), vegetable protein: HR=0.85 (95% CI, 0.75-0.95), fiber: HR =0.81 (95% CI, 0.71-0.93), magnesium: HR=0.77 (95% CI, 0.67-0.89), fruit and vegetables: HR=0.85 (95% CI, 0.74-0.97), whole grain: HR=0.84(95% CI, 0.76-0.93), nuts: HR=0.72 (95% CI, 0.63-0.83), and red and processed meat: HR=1.25 (95% CI, 1.11-0.42) were associated with risk of hypertension. Besides, adherence to the Dietary Approach to Stop Hypertension was strongly inversely associated with incident hypertension: (Q4 versus Q1) HR=0.66 (95% CI, 0.58-0.75). Our results confirmed the association of several nutritional factors intake and incident hypertension and highlighted that adopting a global healthy diet could strongly contribute to the prevention of hypertension.


Changes in phytoplankton composition in response to tides, wind-induced mixing conditions, and freshwater outflows in an urbanised estuarine complex.
Recent reports have shown an increase in potentially harmful phytoplankton in Santos bay (Southeastern Brazilian Coast), located in a highly urbanised estuarine complex. Prediction of blooms is, thus, essential but the phytoplankton community structure in very dynamic regions is difficult to determine. In the present work, we discriminate bloom forming microphytoplankton dominance and their relationship to physical and meteorological variables to look for patterns observed in different tides and seasons. Comparing 8 distinct situations, we found five scenarios of dominance that could be related to winds, tides and rainfall: i) Surfers, diatoms occurring during high surf zone energies; ii) Sinkers, represented by larger celled diatoms during spring tide, after periods of high precipitation rates; iii) Opportunistic mixers, composed of chain forming diatoms with small or elongate cells occurring during neap tides; iv) Local mixers, microplanktonic diatoms and dinoflagellates which occurred throughout the 298 sampling stations; and v) Mixotrophic dinoflagellates, after intense estuarine discharges. Results suggest alterations in the temporal patterns for some bloom-forming species, while others appeared in abundances above safe limits for public health. This approach can also illustrate possible impacts of changes in freshwater discharge in highly urbanised estuaries.


DNA-glycation leads to depurination by the loss of N2-carboxyethylguanine in vitro.
D-Glucose reacts with nucleosides, mainly guanosine, and DNA in a similar way as with proteins, and DNA-bound advanced glycation endproducts (AGE) are formed. Guanosine (Gua) was incubated with D-glucose or dihydroxyacetone (DHA) under variation of temperature and reaction time, and the formation of the glycation products N2-carboxyethylguanosine (CEG) and N2-carboxymethylguanosine (CMG) was monitored by HPLC/DAD. DHA proved to be a very potent glycating agent which specifically produces CEG. When deoxyguanosine (dGua) was glycated under the same conditions, formation of the glycation product N2-carboxyethyldeoxyguanosine (CEdG) resulted in a significant decrease in stability of the N-glycosidic bond. As a consequence more than 25% of CEdG was hydrolysed to give the corresponding guanine derivative CEguanine, whereas unmodified dGua was stable under these conditions. Glycated DNA was then incubated and depurination by the loss of CEguanine was monitored by HPLC. Significant release of CEguanine was observed, whereas free guanine was neither formed from glycated nor from control DNA in detectable amounts. These data suggest that CEdG which is formed during the glycation of DNA in vitro causes increased depurination of DNA and produces abasic sites.


Detection of endoleaks after endovascular repair of abdominal aortic aneurysm: value of unenhanced and delayed helical CT acquisitions.
To assess unenhanced and delayed phase computed tomographic (CT) images combined with arterial phase images for detecting endoleaks after endovascular treatment for abdominal aortic aneurysm (AAA). CT scans were retrospectively evaluated for the presence of endoleaks after endovascular treatment of AAAs in 33 patients with endoleak (positive group) and 40 patients without evidence of endoleak or aneurysm enlargement (negative group). All patients underwent unenhanced and biphasic contrast material-enhanced CT. The CT scans were reviewed in the following combinations: (a) arterial phase and unenhanced scans (uniphasic/unenhanced set), (b) arterial and delayed phase scans only (biphasic set), and (c) arterial and delayed phase scans with unenhanced scans (complete set). Each set was reviewed by two radiologists blinded to the diagnosis of endoleak. Findings were recorded as positive, negative, or indeterminate for endoleak. Within the positive group, endoleaks were diagnosed with the uniphasic/unenhanced, biphasic, and complete image sets in 30 (91%), 32 (97%), and 33 (100%) patients, respectively. With the uniphasic/unenhanced set, three (9%) endoleaks (seen only on delayed phase images) were missed. With the biphasic set, one (3%) endoleak was interpreted as indeterminate. Within the negative group, uniphasic/unenhanced, biphasic, and complete image sets were negative for endoleaks in 100%, 80%, and 100% of patients, respectively. With the biphasic set, results were indeterminate in 20% of cases. A delayed CT acquisition enables detection of additional endoleaks, while an unenhanced acquisition helps eliminate indeterminate results. Thus, both acquisitions contribute to accurate diagnosis of endoleaks when combined with an arterial phase acquisition.


Intracranial pressure monitoring and inpatient mortality in severe traumatic brain injury: A propensity score-matched analysis.
Although intracranial pressure (ICP) monitoring in severe traumatic brain injury (TBI) is recommended by the Brain Trauma Foundation, the benefits remain controversial. We sought to determine the impact of ICP monitor placement on inpatient mortality within a regional trauma system after correcting for selection bias through propensity score matching. Data were collected on all severe TBI cases presenting to 14 trauma centers during the 2-year study period (2009-2010). Inclusion criteria were as follows: blunt injury, Glasgow Coma Scale (GCS) score of 8 or lower in the emergency department, and abnormal intracranial findings on head computed tomography (CT). Two separate multivariate logistic regression models were used to predict ICP monitor placement and inpatient mortality after controlling for demographics, severity of injury, comorbidities, and TBI-specific variables (GCS score, pupil reactivity, international normalized ratio, and nine specific head CT findings). To account for selection bias, we developed a propensity score-matched model to estimate the "true" effect of ICP monitoring on in-hospital mortality. A total of 844 patients met inclusion criteria; 22 died on arrival to the emergency department. Inpatient mortality was 38.8%; 46.0% of the patients underwent ICP monitor placement. Unadjusted mortality rates were significantly lower in the ICP monitoring group (30.7% vs. 45.7%, p < 0.001). ICP monitor placement was positively associated with CT findings of subdural hematoma, intraparenchymal contusion, and mass effect and negatively associated with age, alcoholism, and elevated international normalized ratio. After adjusting for selection bias via propensity score matching, ICP monitor placement was associated with an 8.3 percentage point reduction in the risk-adjusted mortality rate. ICP monitor placement occurred in only 46% of eligible patients but was associated with significantly decreased mortality after adjusting for baseline risk profile and the propensity to undergo monitoring. As the individual impact of ICP monitoring may vary, future efforts must determine who stands to benefit from invasive monitoring techniques. Therapeutic/care management study, level III.


On-demand acid-gated fluorescence switch-on in photo-generated nanospheres.
Herein, we introduce a fast, additive-free, ambient temperature photochemical approach - utilising the novel Diels-Alder cycloaddition of a photo-active ortho-methylbenzaldehyde (oMBA) with a terminal alkyne - for preparing functional acid-sensitive profluorescent nano-/microspheres in one step. Not previously reported, the possibility of applying such a reaction in the context of particle synthesis provides new possibilities for particle design, where multi-step reactivity can be gated into distinct steps. First, a photochemically-gated particle formation step yields a material possessing a reactive, spring-loaded intermediate at every cross-linking point. A second, on-demand step to initiate fluorescence generation subsequently imparts the properties of the chemical transformation to the material itself. The synthesised particles are narrow-disperse with an average diameter ranging from 170-380 nm.


URINARY AMINO-ACETONE EXCRETION IN LEAD WORKERS.
Urinary amino-acetone concentrations were determined in a group of 51 persons with industrial exposure to lead and the findings compared with those obtained from a control group of 27 persons having no exposure to lead.A good correlation was found between delta-aminolaevulinic acid and amino-acetone excretion in the control group but this correlation was not so well defined in the lead-exposed group. In this group excretion of amino-acetone seemed to be better correlated with excretion of delta-aminolaevulinic acid for values less than 0.6 mg.% than with values greater than 0.6 mg.%. All the men concerned in the investigation were employed in dusty occupations. Hypotheses are put forward to attempt to explain the differences in excretion of amino-acetone noted amongst lead workers with high excretion of delta aminolaevulinic acid.Little correlation was found between amino-acetone excretion and that of either porphobilinogen or coproporphyrin.


The higher order factor structure and gender invariance of the Pathological Narcissism Inventory.
The Pathological Narcissism Inventory (PNI) is a recently developed multidimensional inventory for the assessment of pathological narcissism. The authors describe and report the results of two studies that investigate the higher order factor structure and gender invariance of the PNI. The results of the first study indicate that the PNI has a higher order factor structure that conforms to the theoretical structure of pathological narcissism with one factor representing narcissistic grandiosity and the other capturing narcissistic vulnerability. These results uniquely place the PNI as the only measure to broadly assess the two phenotypic themes of pathological narcissism. In the second study, results from tests of measurement invariance indicate that the PNI performs similarly in large samples of men (n = 488) and women (n = 495). These results further establish the psychometric properties of the PNI and suggest that it is well suited for the assessment of pathological narcissism.


Human Motion Tracking Using 3D Image Features with a Long Short-Term Memory Mechanism Model-An Example of Forward Reaching.
Human motion tracking is widely applied to rehabilitation tasks, and inertial measurement unit (IMU) sensors are a well-known approach for recording motion behavior. IMU sensors can provide accurate information regarding three-dimensional (3D) human motion. However, IMU sensors must be attached to the body, which can be inconvenient or uncomfortable for users. To alleviate this issue, a visual-based tracking system from two-dimensional (2D) RGB images has been studied extensively in recent years and proven to have a suitable performance for human motion tracking. However, the 2D image system has its limitations. Specifically, human motion consists of spatial changes, and the 3D motion features predicted from the 2D images have limitations. In this study, we propose a deep learning (DL) human motion tracking technology using 3D image features with a deep bidirectional long short-term memory (DBLSTM) mechanism model. The experimental results show that, compared with the traditional 2D image system, the proposed system provides improved human motion tracking ability with RMSE in acceleration less than 0.5 (m/s2) X, Y, and Z directions. These findings suggest that the proposed model is a viable approach for future human motion tracking applications.


Degloving injury of small intestine.
Self-inflicted stab wounds are seldom very grave. We report a 25-year-old man who inflicted stab wounds with a glass piece under the influence of alcohol. This led to evisceration and later degloving injury to the small bowel. He recovered following surgery.


Exogenous and intracellularly generated sphingosine 1-phosphate can regulate cellular processes by divergent pathways.
S1P (sphingosine 1-phosphate) is the ligand for a family of specific G-protein-coupled receptors that regulate a wide variety of important cellular functions, including vascular maturation, angiogenesis, cell growth, survival, cytoskeletal rearrangements and cell motility. However, S1P also may have intracellular functions. In this review, we discuss two examples that clearly indicate that intracellularly generated and exogenous S1P can regulate biological processes by divergent pathways.


Bone marrow concentrated cell transplantation: rationale for its use in the treatment of human osteochondral lesions.
Bone marrow is one of the best characterized stem cell microenvironments that contains Mesenchymal Stem Cells (MSCs), a rare population of non-hematopoietic stromal cells. MSCs have been indicated as a new option for regenerative medicine because of their ability to differentiate into various lineages such as bone, cartilage and adipose tissue. However, isolation procedures are crucial for the functional activity of the transplanted cells. The use of concentrated bone marrow cells (BMCs) enables a cell population surrounded by its microenvironment (niche) to be implanted while avoiding all the complications related to the in vitro culture. The cells of the niche are able to regulate stem cell behavior through direct physical contact and secreting paracrine factors. The aim of this study was to characterize BMCs in vitro to evaluate their ability to differentiate toward mature cells and try to understand whether there are differences in the chondrogenic and osteogenic potential of cells from patients of different ages. Mononuclear Cells (MNCs) isolated by Ficoll were used as control. Both cell populations were grown in monolayers and differentiated with specific factors and analyzed by histological and molecular biology assays to evaluate the expression of some specific extracellular matrix molecules. The present investigations revealed the ability of BMCs to act as isolated cells. They are able to form colonies and differentiate toward chondrogenic and osteogenic lineages, the latter pathway appearing to be influenced by donor age. The results obtained by this study support the use of BMCs in clinical practice for the repair of osteochondral damage, which might be particularly useful for the one-step procedure allowing cells to be directly implanted in operating room.


GNAS is frequently mutated in both low-grade and high-grade disseminated appendiceal mucinous neoplasms but does not affect survival.
We analyzed a series of 55 disseminated appendiceal mucinous neoplasms treated at our institution for GNAS and KRAS mutations in an attempt to correlate mutation status with clinicopathological findings and patient survival. GNAS mutations (p.R201H, c.602G>A and p.R201C, and c.602C>T) were identified in 17 (31%) of 55 of disseminated mucinous neoplasms and were found in 8 (35%) of 23 low-grade mucinous neoplasms, 7 (37%) of 19 high-grade mucinous adenocarcinomas lacking a signet ring cell component, and 2 (15%) of 13 high-grade mucinous adenocarcinomas with a signet ring cell component. All 7 mucinous adenocarcinomas composed of pure (>95%) signet ring cells harbored wild-type GNAS. There was no significant association between GNAS mutations and sex and age (both with P > .05) or between GNAS mutations and individual adverse histologic features including cytologic grade, destructive invasion, tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cells (all with P > .05). KRAS mutations were identified in 22 (40%) of 55 disseminated mucinous neoplasms. GNAS-mutated disseminated appendiceal mucinous neoplasms more frequently harbored concurrent KRAS mutations compared with GNAS wild-type tumors (65% versus 29%, P = .018). GNAS mutations were not significantly associated with overall survival (both with P > .05). Only overall tumor grade was an independent predictor of overall survival in the multivariate analysis (P = .01). Our results indicate that GNAS mutations are frequently identified in both low-grade and high-grade disseminated appendiceal mucinous neoplasms indicating that GNAS mutation status cannot be used to distinguish between low-grade from high-grade appendiceal mucinous neoplasms.


ACTH-like molecules in gastropod molluscs: a possible role in ancestral immune response and stress.
The presence of immunoreactive ACTH molecules on phagocytic cells from the freshwater snails Planorbarius corneus and Lymnaea stagnalis was shown by cytofluorimetric analysis. The role of ACTH in phagocytosis and in the release of biogenic amines, two biological responses that may be taken as ancestral types of immune response and stress, respectively, has also been evaluated. ACTH markedly increased the phagocytosis of Staphylococcus aureus by P. corneus haemocytes and caused the release of biogenic amines from such cells into the serum. These data, as well as tracing the ancestral physiological role of ACTH, favour the hypothesis that immune and neuroendocrine systems share a common evolutionary origin.


A national survey of nebuliser use.
Nebuliser drug delivery units were reused in 15% of paediatric wards participating in a national survey, while routine servicing and written information was provided by only half the wards issuing home nebulisers. Written information should be developed as a national resource, and further research on optimal cleaning practices is required.


Isotypes of anti-beta2-glycoprotein I antibodies: association with thrombosis in patients with systemic lupus erythematosus.
To evaluate the association between isotypes of anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) and thrombosis and to identify antiphospholipid antibodies (aPL) that are most associated with thrombosis in patients with systemic lupus erythematosus (SLE). IgG anticardiolipin antibody (aCL) and isotypes of anti-beta2-GPI were measured by ELISA, and clinical evidence of thrombosis was analyzed in 270 patients with SLE. IgG, IgM, and IgA anti-beta2-GPI were positive in 38.1, 13.7, and 34.8% of patients, respectively. Patients with a history of thrombosis were significantly more likely to have lupus anticoagulant (LAC), IgG aCL, and the 3 anti-beta2-GPI isotypes. Arterial thrombosis was associated with the presence of IgG aCL and the 3 anti-beta2-GPI isotypes, whereas venous thrombosis was associated with LAC, IgG aCL, and IgA anti-beta2-GPI. In stepwise multivariate logistic regression analysis, the variable that was associated with thrombosis was IgA anti-beta2-GPI. The occurrence of arterial thrombosis was associated with IgG aCL and that of venous thrombosis was related to IgA anti-beta2-GPI in stepwise multivariate analysis. The IgG, IgM, and IgA anti-beta2-GPI titers were closely correlated with IgG aCL titers. The IgA anti-beta2-GPI titers were also significantly correlated with those of IgG and IgM anti-beta2-GPI. The results suggest that anti-beta2-GPI isotypes are related to the occurrence of thrombosis, and measurements of IgA anti-beta2-GPI may be useful for predicting thrombotic episodes in patients with SLE.


Light-responsible DNA hydrogel-gold nanoparticle assembly for synergistic cancer therapy.
Assembled AuNPs in a DNA hydrogel (Dgel) showed strongly coupled plasmon modes, and the Dgel vehicle can co-load anticancer drugs such as doxorubicin (Dox) as a light-controlled releasing cargo by DNA intercalations. Upon laser excitation, local heat shock generation was accompanied by the release of Dox. A highly synergistic combination of thermo- and chemotherapy was demonstrated in cellular and animal models. Our Dgel vehicle can be fragmented after the excitation-induced heat generations, which subsequently causes the dispersion of the AuNPs. Our system may be less toxic because it uses small sizes of AuNPs, and the inherently biocompatible scaffold may reduce the long-term toxicity by rapid clearance.


Is there a role for physician assistants in community mental health?
The authors briefly describe the history and development of the medical discipline of physician assistants (PAs). A careful review of the literature reveals the limited use of PAs in psychiatry, usually only for primary health care needs. A model for using PAs as psychiatric assistants is presented, including the training required and a description of the clinical and administrative functions. The advantages of such a model are multiple. These include: 1) more effective and efficient use of the psychiatrist; 2) reduced costs of service; 3) increased primary medical screening capability in the CMHC; and 4) increased presence of ethnic minorities on the professional staff of the CMHC. Disadvantages of the model relate to training and "turf" issues. In view of the shortage and dissatisfaction of psychiatrists in CMHC settings, and other challenges to the provision of quality mental health care in the community, this model should be considered as a logical and positive response to that challenge. If the model is valid, then training facilities must make a systematic effort to recruit, train, and place psychiatric physician assistants in community agencies.


Cellular eukaryotic initiation factor 5A content as a mediator of polyamine effects on growth and apoptosis.
The polyamines are essential for eukaryotic cell growth. One of the most critical effects of polyamines on cell growth is the availability of spermidine for the post-translational modification of eIF-5A. Because hypusine-containing eIF-5A is necessary for cell proliferation, depletion of cellular polyamines suppresses growth by depleting cellular modified eIF-5A content. Excess putrescine accumulations in DH23A/b cells induces apoptosis and suppresses the formation of hypusine-containing eIF-5A. Treatment of DH23A/b cells with diaminoheptane also suppresses modified eIF-5A formation and induces apoptosis. These data suggest that suppression of modified eIF-5A formation may play a role in putrescine-induced apoptosis as well.


A Rare Case of Systemic Mastocytosis With Associated Clonal Hematological Non-Mast Cell Lineage Disease That Transformed to Acute Leukemia With IDH2 Mutation.
An elderly 72-year-old man presented with anemia, thrombocytopenia, monocytosis, splenomegaly and lymphadenopathy. Bone marrow biopsy was consistent with mast cell neoplasm with positive CD117, CD25, CD34 myeloblasts and polymerase chain reaction (PCR) revealed mutation of D816V. He developed bilateral femoral neck fractures and biopsy confirmed that he has systemic mastocytosis (SM). He received cladribine and midostaurin with stable disease for 21 months. His SM with associated clonal hematological non-mast cell lineage disease (SM-AHNMD) transformed to acute myelogenous leukemia with isocitrate dehydrogenase 2 (IDH2) mutation. A trial of enasidenib was given for 5 months but without any response. Patient decided to go with home hospice and died afterwards.


Emerging tumor entities and variants of CNS neoplasms.
Since the appearance in 2000 of the World Health Organization (WHO) classification for central nervous system (CNS) neoplasms, numerous descriptions of new entities or variants have appeared in the literature. In the group of neuronal and mixed glioneuronal neoplasms are lesions with distinctive morphological features that are still not included in a precise classification, including extraventricular neurocytoma, papillary glioneuronal tumor, rosette-forming glioneuronal of the fourth ventricle, glioneuronal with neuropil-like rosette, and DNT-like tumor of the septum pellucidum. The glioneuronal tumor with neuropil-like rosette and oligodendroglioma with neurocytic differentiation represent morphological variants of genetically proven diffuse gliomas. The lipoastrocytoma and the pilomixoid astrocytoma enlarge the group of astrocytic lesions. Rare, low-grade gliomas of the spinal cord with extensive leptomeningeal dissemination associated with unusual neuroimaging are described. The chordoid glioma of the third ventricle and the papillary tumor of the pineal region seem to be correlated by a common histogenesis from the specialized ependyma of the subcommissural organ. An embryonal tumor with neuropil and true rosettes combining features of neuroblastoma and ependymoblastoma is discussed. These new, recently described lesions indicate that the complex morphologic spectrum of CNS tumors is far from being completely delineated.


Single-cell DNA from West Greenland marine sediments suggests presence of Protoperidinium tricingulatum in the Arctic.
Spiny brown dinoflagellate cysts are commonly used as sea-ice indicators in the Arctic, but their biological affinities are not well known. We present the first indication of hitherto temperate Protoperidinium tricingulatum in the Arctic based on single-cell LSU rDNA sequencing from sediments of the Disko Bay-Vaigat Sound, West Greenland. The morphological similarity of the sequenced cyst morphotype to the sea-ice indicator Islandinium? cezare morphotype 1 is striking. The morphology of the isolated cysts, as well as those observed in the total cyst assemblage following standard palynological preparation, both resemble either I.? cezare morphotype 1 or P. tricingulatum, suggesting that the specimens may in fact be close morphological variants of the same species. In addition, nine LSU rDNA sequences were obtained from morphological variants assigned to Islandinium minutum s.l.: including both subspecies minutum and subspecies barbatum. The two subspecies could not be differentiated based on partial LSU rDNA sequencing. Overall, Arctic spiny brown dinoflagellate cyst species may be morphologically more diverse and taxonomically more complex than shown earlier and further genetic and morphological studies are needed. Importantly, the value of cysts as palaeoecological indicators depends on a sound understanding of their biological affinity and taxonomy.


Quantifying in vitro growth and metabolism kinetics of human mesenchymal stem cells using a mathematical model.
Better quantitative understanding of human mesenchymal stem cells (hMSCs) metabolism is needed to identify, understand, and subsequently optimize the processes in expansion of hMSCs in vitro. For this purpose, we analyzed growth of hMSCs in vitro with a mathematical model based on the mass balances for viable cell numbers, glucose, lactate, glutamine, and glutamate. The mathematical modeling had two aims: (1) to estimate kinetic parameters of important metabolites for hMSC monolayer cultures, and (2) to quantitatively assess assumptions on growth of hMSCs. Two cell seeding densities were used to investigate growth and metabolism kinetics of MSCs from three human donors. We analyzed growth up to confluency and used metabolic assumptions described in literature. Results showed a longer initial phase, a slower growth rate, and a higher glucose, lactate, glutamine, and glutamate metabolic rates at the lower cell seeding density. Higher metabolic rates could be induced by a lower contact inhibition effect when seeding at 100 cells/cm2 than when seeding at 1000 cells/cm2. In addition, parameter estimation describing kinetics of hMSCs in culture, depending on the seeding density, showed doubling times in the order of 17-32h, specific glucose consumption in the order of 1.25 x 10(-1) to 3.77 x 10(-1) pmol/cell/h, specific lactate production in the order of 2.48 x 10(-1) to 7.67 x 10(-1)pmol/cell/h, specific glutamine production in the order of 7.04 x 10(-3) to 2.27 pmol/cell/h, and specific glutamate production in the order of 4.87 x 10(-1) to 23.4 pmol/cell/h. Lactate-to-glucose yield ratios confirmed that hMSCs use glucose via anaerobic glycolysis. In addition, glutamine and glutamate metabolic shifts were identified that could be important for understanding growth of hMSCs in vitro. This study showed that the mathematical modeling approach supports quantitative analysis of important mechanisms in proliferation of hMSCs in vitro.


Merocyanine 540 as an optical probe of transmembrane electrical activity in the heart.
Frog hearts stained with merocyanine 540 shows a 1.5 to 2.0 percent increase in fluorescence intensity at 585 nanometers during the cardiac action potential when excited with a 540-nonometer light beam. Fluorometric action potentials similar to those recorded with intracellular microelectrodes in pacemaker, atrial, and ventricular tissues were recorded by focusing a 1-millimeter excitation beam on various regions of the heart. The signal-to-noise ratio for a single action potential ranged between 10/1 and 40/1. In spontaneously pacing hearts the slower rate of rise of the fluorescence action potential is due to the slow propagation of the electrical signal. In solutions containing normal calcium concentrations the fluorometric signal is altered by contractions. Merocyanine 540 is biologically inert as it stains the cardiac cell membrane and acts as a sensitive optical probe of the change in transmembrane potential.


Automated cerebral infarct volume measurement in follow-up noncontrast CT scans of patients with acute ischemic stroke.
Cerebral infarct volume as observed in follow-up CT is an important radiologic outcome measure of the effectiveness of treatment of patients with acute ischemic stroke. However, manual measurement of CIV is time-consuming and operator-dependent. The purpose of this study was to develop and evaluate a robust automated measurement of the CIV. The CIV in early follow-up CT images of 34 consecutive patients with acute ischemic stroke was segmented with an automated intensity-based region-growing algorithm, which includes partial volume effect correction near the skull, midline determination, and ventricle and hemorrhage exclusion. Two observers manually delineated the CIV. Interobserver variability of the manual assessments and the accuracy of the automated method were evaluated by using the Pearson correlation, Bland-Altman analysis, and Dice coefficients. The accuracy was defined as the correlation with the manual assessment as a reference standard. The Pearson correlation for the automated method compared with the reference standard was similar to the manual correlation (R = 0.98). The accuracy of the automated method was excellent with a mean difference of 0.5 mL with limits of agreement of -38.0-39.1 mL, which were more consistent than the interobserver variability of the 2 observers (-40.9-44.1 mL). However, the Dice coefficients were higher for the manual delineation. The automated method showed a strong correlation and accuracy with the manual reference measurement. This approach has the potential to become the standard in assessing the infarct volume as a secondary outcome measure for evaluating the effectiveness of treatment.


Current problems in the diagnosis and management of chronic active hepatitis.
Although corticosteroids have been shown to be effective in the treatment of most forms of severe chronic active hepatitis, many problems remain in the diagnosis and management of patients with this disease. Difficulties in determining chronicity, establishing the correct diagnosis, and deciding when and how to initiate and stop therapy jeopardize successful management. Mechanisms of drug action, pharmacokinetics, long-term sequelae of therapy, and optimum treatment schedules have been incompletely described. A satisfactory program of management remains undefined for patients with less than severe disease, hepatitis B surface antigenemia, and suboptimal results after conventional treatment. The goals of this review are to identify problem areas and to indicate directions for future investigation and improvement.


Sodium salicylate interferes with the inhibitory effects of aspirin and indomethacin on human platelets.
The interference of sodium salicylate with the effects of acetylsalicylic acid (ASA, aspirin) and indomethacin on arachidonic acid-induced platelet aggregation and thromboxane formation was studied in human platelet rich plasma. ASA and indomethacin suppressed both aggregation and the concomitant formation of thromboxane B2 whereas sodium salicylate alone had no significant effect on these parameters of platelet function. It did, however, partially prevent the inhibitory effects of ASA and indomethacin on platelet aggregation when it was added to platelet rich plasma before ASA or indomethacin. The inhibition of thromboxane formation by indomethacin was also prevented by sodium salicylate. When sodium salicylate was added to platelet rich plasma after ASA or indomethacin it did not modify the effects of these drugs. The present study indicates that sodium salicylate interferes with the effects of ASA and indomethacin on human platelet cyclo-oxygenase in vitro.


Does Antihypertensive Drug Class Affect Day-to-Day Variability of Self-Measured Home Blood Pressure? The HOMED-BP Study.
Recent literature suggests that blood pressure variability (BPV) predicts outcome beyond blood pressure level (BPL) and that antihypertensive drug classes differentially influence BPV. We compared calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockade for effects on changes in self-measured home BPL and BPV and for their prognostic significance in newly treated hypertensive patients. We enrolled 2484 patients randomly allocated to first-line treatment with a calcium channel blocker (n=833), an angiotensin-converting enzyme inhibitor (n=821), or angiotensin receptor blockade (n=830). Home blood pressures in the morning and evening were measured for 5 days off treatment before randomization and for 5 days after 2 to 4 weeks of randomized drug treatment. We assessed BPL and BPV changes as estimated by variability independent of the mean and compared cardiovascular outcomes. Home BPL response in each group was significant (P≤0.0001) but small in the angiotensin-converting enzyme inhibitor group (systolic/diastolic: 4.6/2.8 mm Hg) compared with the groups treated with a calcium channel blocker (systolic/diastolic: 8.3/3.9 mm Hg) and angiotensin receptor blockade (systolic/diastolic: 8.2/4.5 mm Hg). In multivariable adjusted analyses, changes in home variability independent of the mean did not differ among the 3 drug classes (P≥0.054). Evening variability independent of the mean before treatment significantly predicted hard cardiovascular events independent of the corresponding home BPL (P≤0.022), whereas BPV did not predict any cardiovascular outcome based on the morning measurement (P≥0.056). Home BPV captured after monotherapy had no predictive power for cardiovascular outcome (P≥0.22). Self-measured home evening BPV estimated by variability independent of the mean had prognostic significance, whereas antihypertensive drug classes had no significant impact on BPV changes. Home BPL should remain the primary focus for risk stratification and treatment. URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000137.


Selective elimination of aphid endosymbionts: effects of antibiotic dose and host genotype, and fitness consequences.
Multiple endosymbionts commonly coexist in the same host insects. In order to gain an understanding of the biological roles of the individual symbionts in such complex systems, experimental techniques for enabling the selective removal of a specific symbiont from the host are of great importance. By using the pea aphid-Buchnera-Serratia endosymbiotic system as a model, the efficacy, generality, and fitness consequences of selective elimination techniques at various antibiotic doses and under a variety of host genotypes were investigated. In all the disymbiotic aphid strains examined, the facultative symbiont Serratia was selectively eliminated by ampicillin treatment in a dose-dependent manner, suggesting a generality of the elimination technique irrespective of host genotype. However, fitness consequences of the Serratia elimination differed between the aphid strains, indicating substantial effects of host genotype. In all the disymbiotic aphid strains, the obligate symbiont Buchnera was selectively eliminated by rifampicin treatment irrespective of the antibiotic dose. However, the survival and reproduction of the Buchnera-free aphids varied in a dose-dependent manner, and the dose dependence was strikingly different between the aphid genotypes. These results provide a basis for the development of new protocols for manipulating insect endosymbiotic microbiota.


Genetic variation at MHC class II loci influences both olfactory signals and scent discrimination in ring-tailed lemurs.
Diversity at the Major Histocompatibility Complex (MHC) is critical to health and fitness, such that MHC genotype may predict an individual's quality or compatibility as a competitor, ally, or mate. Moreover, because MHC products can influence the components of bodily secretions, an individual's body odors may signal its MHC composition and influence partner identification or mate choice. Here, we investigated MHC-based signaling and recipient sensitivity by testing for odor-gene covariance and behavioral discrimination of MHC diversity and pairwise dissimilarity in a strepsirrhine primate, the ring-tailed lemur (Lemur catta). First, we coupled genotyping of the MHC class II gene, DRB, with gas chromatography-mass spectrometry of genital gland secretions to investigate if functional genetic diversity is signaled by the chemical diversity of lemur scent secretions. We also assessed if the chemical similarity between individuals correlated with their MHC-DRB similarity. Next, we assessed if lemurs discriminated this chemically encoded, genetic information in opposite-sex conspecifics. We found that both sexes signaled overall MHC-DRB diversity and pairwise MHC-DRB similarity via genital secretions, but in a sex- and season-dependent manner. Additionally, the sexes discriminated absolute and relative MHC-DRB diversity in the genital odors of opposite-sex conspecifics, suggesting that lemur genital odors function to advertise genetic quality. In summary, genital odors of ring-tailed lemurs provide honest information about an individual's absolute and relative MHC quality. Complementing evidence in humans and Old World monkeys, we suggest that reliance on scent signals to communicate MHC quality may be important across the primate lineage.


Genetic isolates in East Asia: a study of linkage disequilibrium in the X chromosome.
The background linkage disequilibrium (LD) in genetic isolates is of great interest in human genetics. Although many empirical studies have evaluated the background LD in European isolates, such as the Finnish and Sardinians, few data from other regions, such as Asia, have been reported. To evaluate the extent of background LD in East Asian genetic isolates, we analyzed the X chromosome in the Japanese population and in four Mongolian populations (Khalkh, Khoton, Uriankhai, and Zakhchin), the demographic histories of which are quite different from one another. Fisher's exact test revealed that the Japanese and Khalkh, which are the expanded populations, had the same or a relatively higher level of LD than did the Finnish, European American, and Sardinian populations. In contrast, the Khoton, Uriankhai, and Zakhchin populations, which have kept their population size constant, had a higher background LD. These results were consistent with previous genetic anthropological studies in European isolates and indicate that the Japanese and Khalkh populations could be utilized in the fine mapping of both complex and monogenic diseases, whereas the Khoton, Uriankhai, and Zakhchin populations could play an important role in the initial mapping of complex disease genes.


A genome-wide meta-analysis of association studies of Cloninger's Temperament Scales.
Temperament has a strongly heritable component, yet multiple independent genome-wide studies have failed to identify significant genetic associations. We have assembled the largest sample to date of persons with genome-wide genotype data, who have been assessed with Cloninger's Temperament and Character Inventory. Sum scores for novelty seeking, harm avoidance, reward dependence and persistence have been measured in over 11,000 persons collected in four different cohorts. Our study had >80% power to identify genome-wide significant loci (P<1.25 × 10(-8), with correction for testing four scales) accounting for ≥0.4% of the phenotypic variance in temperament scales. Using meta-analysis techniques, gene-based tests and pathway analysis we have tested over 1.2 million single-nucleotide polymorphisms (SNPs) for association to each of the four temperament dimensions. We did not discover any SNPs, genes, or pathways to be significantly related to the four temperament dimensions, after correcting for multiple testing. Less than 1% of the variability in any temperament dimension appears to be accounted for by a risk score derived from the SNPs showing strongest association to the temperament dimensions. Elucidation of genetic loci significantly influencing temperament and personality will require potentially very large samples, and/or a more refined phenotype. Item response theory methodology may be a way to incorporate data from cohorts assessed with multiple personality instruments, and might be a method by which a large sample of a more refined phenotype could be acquired.


Abcc6 deficiency prevents rhabdomyolysis-induced acute kidney injury.
Rhabdomyolysis is a risk factor for acute kidney injury, transition towards chronic kidney disease, and death. The role of calcium phosphate deposits in the mechanisms of rhabdomyolysis-induced acute kidney injury (RAKI) is still unclear. Better insight of the role calcium in RAKI could lead to new therapeutic avenues. Here, we show in a mice model of RAKI that calcium phosphate deposits were frequent in the kidney (hydroxyapatite) and partly correlated with the severity of the kidney injury. However, the intensity of deposits was highly heterogeneous between mice. Treatment with sodium chloride, sodium bicarbonate or inorganic pyrophosphate (PPi; an inhibitor of the calcium phosphate crystallization), or combinations thereof, did not improve kidney outcomes and hydroxyapatite deposition during RAKI. Unexpectedly, Abcc6 knockout mice (ko), characterized by PPi deficiency, developed less severe RAKI despite similar rhabdomyolysis severity, and had similar hydroxyapatite deposition suggesting alternative mechanisms. This improved kidney outcome at day 2 translated to a trend in improved glomerular filtration rate at month 2 in Abcc6-/-mice and to significantly less interstitial fibrosis. In addition, whereas the pattern of infiltrating cells at day 2 was similar between wt and ko mice, kidneys of Abcc6-/- mice were characterized by more CD19+ B-cells, less CD3+ T-cells and a lower R1/R2 macrophage ratio at month 2. In summary, kidney calcium phosphate deposits are frequent in RAKI but hydration with sodium bicarbonate or sodium chloride does not modify the kidney outcome. Blocking ABCC6 emerges as a new option to prevent RAKI and subsequent transition toward kidney fibrosis.


Effects of low cell pH and elevated inorganic phosphate on the pCa-force relationship in single muscle fibers at near-physiological temperatures.
Intense muscle contraction induces high rates of ATP hydrolysis with resulting increases in Pi, H(+), and ADP, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at 15 and 30°C. At 30°C, pH 6.2 + 30 mM Pi significantly depressed peak force in all fiber types, with the greatest effect in type IIx fibers. Across fiber types, Ca(2+) sensitivity was depressed by low pH and low pH + high Pi, with the greater effect at 30°C. For type IIx fibers at 30°C, half-maximal activation (pCa50) was 5.36 at pH 6.2 (no added Pi) and 4.98 at pH 6.2 + 30 mM Pi compared with 6.58 in the control condition (pH 7, no added Pi). At 30°C, n2, reflective of thick filament cooperativity, was unchanged by low cell pH but was depressed from 5.02 to 2.46 in type IIx fibers with pH 6.2 + 30 mM Pi. With acidosis, activation thresholds of all fiber types required higher free Ca(2+) at 15 and 30°C. With the exception of type IIx fibers, the Ca(2+) required to reach activation threshold increased further with added Pi. In conclusion, it is clear that fatigue-inducing effects of low cell pH and elevated Pi at near-physiological temperatures are substantial.


A high-throughput dielectrophoresis-based cell electrofusion microfluidic device.
A high-throughput cell electrofusion microfluidic chip has been designed, fabricated on a silicon-on-insulator wafer and tested for in vitro cell fusion under a low applied voltage. The developed chip consists of six individual straight microchannels with a 40-μm thickness conductive highly doped Si layer as the microchannel wall. In each microchannel, there are 75 pairs of counter protruding microelectrodes, between which the cell electrofusion is performed. The entire highly doped Si layer is covered by a 2-μm thickness aluminum film to maintain a consistent electric field between different protruding microelectrode pairs. A 150-nm thickness SiO₂ film is subsequently deposited on the top face of each protruding microelectrode for better biocompatibility. Owing to the short distance between two counter protruding microelectrodes, a high electric field can be generated for cell electrofusion with a low voltage imposed across the electrodes. Both mammalian cells and plant protoplasts were used to test the cell electrofusion. About 42-68% cells were aligned to form cell-cell pairs by the dielectrophoretic force. After cell alignment, cell pairs were fused to form hybrid cells under the control of cell electroporation and electrofusion signals. The averaged fusion efficiency in the paired cells is above 40% (the highest was about 60%), which is much higher than the traditional polyethylene glycol method (<5%) and traditional electrofusion methods (∼12%). An individual cell electrofusion process could be completed within 10 min, indicating a capability of high throughput.


Grayanotoxin poisoning in three goats.
Six Nubian goats were exposed to an azalea branch (Rhododendron indica) at the Riverbanks Zoological Park in Columbia, South Carolina. The following day, 3 of the 6 goats were referred to the veterinary hospital of the Riverbanks Zoological Park with bloat, profuseregurgitation, and signs of depression, intermittent head pressing, and fine muscle tremors in the hind limbs. The goats were treated with magnesium hydroxide, activated charcoal, and lactated Ringer's solution and recovered within 24 hours. Definitive diagnosis of grayanotoxin exposure was accomplished by use of liquid chromatography-mass spectrometry analysis of urine and fecal samples. Rhododendron spp are members of the Ericaceae (Heath) family and may contain grayanotoxins, which exert toxic effects by binding to sodium channels in cell membranes and increasing the permeability of sodium ions in excitable membranes. Rhododendron poisoning should be considered in animals with clinical evidence of gastrointestinal tract irritation, cardiac arrhythmias, and neurologic signs.


Topology of the C-terminal tail of HIV-1 gp41: differential exposure of the Kennedy epitope on cell and viral membranes.
The C-terminal tail (CTT) of the HIV-1 gp41 envelope (Env) protein is increasingly recognized as an important determinant of Env structure and functional properties, including fusogenicity and antigenicity. While the CTT has been commonly referred to as the "intracytoplasmic domain" based on the assumption of an exclusive localization inside the membrane lipid bilayer, early antigenicity studies and recent biochemical analyses have produced a credible case for surface exposure of specific CTT sequences, including the classical "Kennedy epitope" (KE) of gp41, leading to an alternative model of gp41 topology with multiple membrane-spanning domains. The current study was designed to test these conflicting models of CTT topology by characterizing the exposure of native CTT sequences and substituted VSV-G epitope tags in cell- and virion-associated Env to reference monoclonal antibodies (MAbs). Surface staining and FACS analysis of intact, Env-expressing cells demonstrated that the KE is accessible to binding by MAbs directed to both an inserted VSV-G epitope tag and the native KE sequence. Importantly, the VSV-G tag was only reactive when inserted into the KE; no reactivity was observed in cells expressing Env with the VSV-G tag inserted into the LLP2 domain. In contrast to cell-surface expressed Env, no binding of KE-directed MAbs was observed to Env on the surface of intact virions using either immune precipitation or surface plasmon resonance spectroscopy. These data indicate apparently distinct CTT topologies for virion- and cell-associated Env species and add to the case for a reconsideration of CTT topology that is more complex than currently envisioned.


Reaction-rate theory with account of the crystal anharmonicity.
Reaction rate theory in solids is modified taking into account intrinsic localized modes or discrete breathers (DBs) that can appear in crystals with sufficient anharmonicity, resulting in violation of Arrhenius' law. Large-amplitude oscillations of atoms about their equilibrium positions in the lattice cause local potentials of alternating sign, which are described in terms of time-periodic modulations of the potential barriers for chemical reactions taking place in the vicinity of DBs. The reaction rate averaged over large macroscopic volumes and times including many DBs is increased by a factor that depends on the DB statistics. The breather statistics in thermal equilibrium and in thermal spikes in solids under irradiation with swift particles is considered, and the corresponding reaction rate amplification factors are derived.


Open access journals are as likely to be referenced by the Orthopaedic literature, despite having a lower impact factor than subscription-based journals.
The internet has changed the way we access and publish Orthopaedic literature. Traditional subscription journals have been challenged by the open access method of publication which permits the author to make their article available to all readers for free, often at a cost to the author. This has also been adopted in part by traditional subscription journals forming hybrid journals. One of the criticisms of open access publications is that it provides the author with a "pay to publish" opportunity. We aimed to determine if access to the journals impacts their influence. We selected the top 40 Trauma and Orthopaedic Journals as ranked by the SCImago Rank. Each journal was reviewed and assessed for the journal quality, defined by reviewing the journal impact factor and SCImago rank; influence, defined by reviewing the top 10 articles provided by the journal for the number of citations; and cost of open access publication. Of the top 40 journals, 10 were subscription, 10 were open access, and 20 were hybrid journals. Subscription journals had the highest mean impact factor, and SCImago rank with a significant difference in the impact factor (p = 0.001) and SCImago rank (p = 0.021) observed between subscription and open access journals. No significant difference was seen between citation numbers of articles published in subscription and open access journals (p = 0.168). There was a positive correlation between the cost of publishing in an open access journal and the impact factor (r = 0.404) but a negative correlation between cost and the number of citations (r = 0.319). Open access journals have significantly lower quality measures in comparison to subscription journals. Despite this, we found no difference between the number of citations, suggestive of there being no difference in the influence of these journals in spite of the observed difference in quality.


Disseminated intravascular coagulation in a case of brucellosis.
Brucellosis is a multisystem disease with a broad spectrum of clinical manifestations; hematological abnormalities ranging from fulminant as of disseminated intravascular coagulation (DIC) to anaemia, leucopoenia, thrombocytopenia, and clotting disorders. In this report, we present DIC in a case of brucellosis because of rare presentation. A 3-year-old boy was admitted with the complaints of continuous fever, vomiting, abdominal pain, and bruise on leg. He looked pale and his physical examination revealed purpuric skin lesions on both legs. A mild hepatosplenomegaly was noted on palpation. Laboratory tests showed hematocrit 21%, hemoglobin 7 g/dL, platelet count 20,000/mm(3), prothrombin time 19 seconds, activated partial thromboplastin time 48 seconds, plasma fibrinogen level 20 mg/dL, and D-dimer 8 µg/mL. Serum antibrucella titration agglutination test was found to be 1 of 1280 positive. Blood cultures performed on specimens obtained at the time of admission yielded Brucella melitensis. The clinical and laboratory findings were consistent with DIC.


Sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition.
Basal-like breast cancer (BLBC) remains a great challenge because of its clinically aggressive nature and lack of effective targeted therapy. We analyzed the potential anti-neoplastic effects of sanguinarine, a natural benzophenanthridine alkaloid, against BLBC cells. Sanguinarine treatment resulted in a reduction of cell migration, in a dose-dependent inhibition of cell viability and in the induction of cell death by apoptosis in both human (MDA-MB-231 cells) and mouse (A17 cells) in vitro models of BLBC. In vivo experiments demonstrated that oral administration of sanguinarine reduced the development and growth of A17 transplantable tumors in FVB syngeneic mice. Western blotting analysis revealed that suppression of BLBC growth by sanguinarine was correlated with a concurrent upregulation of p27 and downregulation of cyclin D1 and with the inhibition of STAT3 activation. In addition, we identified sanguinarine as a potent inhibitor of dihydrofolate reductase (DHFR), able to impair enzyme activity even in methotrexate resistant MDA-MB-231 cells. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC.


Association between decreased thyroid stimulating hormone and hyperuricemia in type 2 diabetic patients with early-stage diabetic kidney disease.
Serum uric acid (SUA) is associated with the development of diabetic kidney disease (DKD). Thyroid hormones can regulate metabolism and insulin resistance. The relationship between SUA and thyroid function in patients with DKD is still uncertain. In current study, we aimed to investigate the association between thyroid stimulating hormone (TSH) and SUA in type 2 diabetic patients with early-stage DKD. Two hundred fifty-four type 2 diabetic patients with early-stage DKD were enrolled in current study and were further classified as high SUA group (SUA level > 420 μmol/L in males or > 360 μmol/L in females, n = 101) and normal SUA group (SUA level ≤ 420 μmol/L in males or ≤ 360 μmol/L in females, n = 153). Eighty-five control subjects were recruited as control group. The clinical characteristics were obtained via face-to-face surveys and medical records. Compared with normal SUA group and control group, high SUA group exhibited the increased SUA level, and the decreased TSH level (P < 0.017 for all), and no significant difference was detected in SUA and TSH between normal SUA group and control group. TSH was negatively associated with SUA (r = - 0.35, P < 0.001) in type 2 diabetic participants with early-stage DKD. Furthermore, the decreased TSH level was independently correlated with higher SUA level (β = - 25.69, P < 0.001), and retained a significant association with hyperuricemia (odds ratio = 1.73, P = 0.002) after adjusting for confounding factors in type 2 diabetic patients with early-stage DKD. TSH is negatively correlated with SUA, and decreased TSH is an independent risk factor for hyperuricemia in type 2 diabetic patients with early-stage DKD. These results indicate that thyroid hormones, TSH in particular, might participate in regulating uric acid metabolism in patients with early-stage DKD.


Phase 1 clinical trial of Vesicare™ (solifenacin) in the treatment of urinary incontinence after radical prostatectomy.
Permanent and prolonged incontinence following robot assisted radical prostatectomy (RARP) is known to result from injury to the external sphincter. We hypothesize that pre-existing detrusor overactivity may also contribute to delayed return of continence (>3 months). This pilot study examines the safety profile and efficacy of muscarinic receptor antagonist, solifenacin, in incontinent men after prostatectomy. Men using three or more pads 7 days post catheter removal were invited to enroll into the study (5 mg daily of solifenacin for 3 months). All subjects received RARP under hypothermic conditions by one surgeon. Continence was defined as 0 pads. Forty men were enrolled, one excluded due to missing follow-up. Two men reported nonserious adverse events: one a vaso-vagal reaction when taking solifenacin with sildenafil, and the other was dehydration and dizziness after strenuous exercise. Additionally, four withdrew due to side effects. The efficacy outcomes show improved intermittency after prostatectomy, though unclear if due to the medication. At 3 months, 21 patients (53.8%) reached the primary continence outcome of zero pads. The median time to continence in this group was 95 days. Solifenacin is well tolerated in post radical prostatectomy patients with a 15% withdrawal rate due to side effects. These results formed the basis of a large, prospectively randomized clinical trial comparing the effects of solifenacin versus placebo in a population of men incontinent after RARP.


The structure and function of bacterial light-harvesting complexes.
The harvesting of solar radiation by purple photosynthetic bacteria is achieved by circular, integral membrane pigment-protein complexes. There are two main types of light-harvesting complex, termed LH2 and LH1, that function to absorb light energy and to transfer that energy rapidly and efficiently to the photochemical reaction centres where it is trapped. This mini-review describes our present understanding of the structure and function of the purple bacterial light-harvesting complexes.


Spatial heterogeneity and irreversible vegetation change in semiarid grazing systems.
Recent theoretical studies have shown that spatial redistribution of surface water may explain the occurrence of patterns of alternating vegetated and degraded patches in semiarid grasslands. These results implied, however, that spatial redistribution processes cannot explain the collapse of production on coarser scales observed in these systems. We present a spatially explicit vegetation model to investigate possible mechanisms explaining irreversible vegetation collapse on coarse spatial scales. The model results indicate that the dynamics of vegetation on coarse scales are determined by the interaction of two spatial feedback processes. Loss of plant cover in a certain area results in increased availability of water in remaining vegetated patches through run-on of surface water, promoting within-patch plant production. Hence, spatial redistribution of surface water creates negative feedback between reduced plant cover and increased plant growth in remaining vegetation. Reduced plant cover, however, results in focusing of herbivore grazing in the remaining vegetation. Hence, redistribution of herbivores creates positive feedback between reduced plant cover and increased losses due to grazing in remaining vegetated patches, leading to collapse of the entire vegetation. This may explain irreversible vegetation shifts in semiarid grasslands on coarse spatial scales.


Outbreak of Septic Arthritis Associated with Intra-Articular Injections at an Outpatient Practice - New Jersey, 2017.
On March 6, 2017, the New Jersey Department of Health (NJDOH) was notified of three cases of septic arthritis in patients who had received intra-articular injections for osteoarthritic knee pain at a private outpatient practice. The practice voluntarily closed the next day. NJDOH, in conjunction with the local health department and the New Jersey Board of Medical Examiners, conducted an investigation and identified 41 cases of septic arthritis associated with intra-articular injections administered during 250 patient visits at the same practice, including 30 (73%) patients who required surgery. Bacterial cultures of synovial fluid or tissue from 15 (37%) patients were positive; all recovered organisms were oral flora. An infection prevention assessment of the practice identified multiple breaches of recommended infection prevention practices, including inadequate hand hygiene, inappropriate use of pharmacy bulk packaged (PBP) products as multiple-dose containers and handling PBP products outside of required pharmacy conditions, and preparation of syringes up to 4 days in advance of their intended use. No additional septic arthritis cases were identified after infection prevention recommendations were implemented within the practice.


Type II diabetes mellitus.
Type II diabetes is a common disorder whose prevalence is increasing in the United States and throughout the world. Type II diabetes is also associated with several other metabolic abnormalities such as central obesity, hypertension, and dyslipidemia, which contributes to the very high rate of cardiovascular morbidity and mortality. The main pathologic defects in diabetes consist of excessive hepatic glucose production, peripheral insulin resistance, and defective beta-cell secretory function. The duration and severity of the hyperglycemia dictate the microvascular complications, no matter what the etiology of the glucose intolerance, and the goals of therapy should be similar to those of insulin-dependent type I diabetic patients. Initiation of nonpharmacologic therapy should be started as soon as the diagnosis is made. Pharmacologic agents should be initiated if the glycemic goals are not met with a 3-month trial of diet and exercise. The cornerstone of therapy consists of a regular exercise routine along with a diet consisting of 40% to 50% complex carbohydrates, 10% to 20% protein, and monounsaturated fats such as canola oil and olive oil. If nonpharmacologic therapy does not achieve adequate glycemic control, initiation of an oral antidiabetic agent is warranted. In addition to the sulfonylureas, which work by stimulating insulin secretion, we now have metformin, which inhibits excessive hepatic glucose production; acarbose, which delays the absorption of carbohydrates in the gut; and troglitazone, which reduces insulin, resistance primarily in skeletal muscle. The selection of an initial oral antidiabetic agent depends on patient characteristics such as the presence of obesity and dyslipidemia, the duration of diabetes, and other concomitant conditions. Combination therapy with two or three of the different classes of oral antidiabetic agents is effective and has been used throughout the world. When maximum doses of oral antidiabetic agents do not adequately control glycemia, insulin therapy is necessary. In selected patients, combination therapy consisting of bedtime intermediate-acting insulin in addition to daytime oral antidiabetic agent(s) can be an effective method to normalize glucose control without the need for rigorous insulin regimens. When combination therapy fails, a split-mixed regimen using premixed 70/30 insulin prebreakfast and predinner can be very effective in obese subjects. In thin insulin-requiring subjects with type II diabetes, more intensive regimens may be required. In general, the risk of severe hypoglycemia is quite low in patients with type II diabetes, and the main adverse effect of insulin therapy is weight gain. Prevention and aggressive treatment of glucose intolerance and the other adverse metabolic conditions associated with type II diabetes will not only have a positive effect on the quality of life but also provide long-term cost savings.


Diclofenac potassium 12.5mg tablets for mild to moderate pain and fever: a review of its pharmacology, clinical efficacy and safety.
Non-prescription (over-the-counter [OTC]) analgesics are used for the short-term treatment of acute painful conditions of mild to moderate intensity in everyday life. Well documented safety and efficacy, a rapid onset of action and a flexible daily dosing regimen are essential in this context. Film-coated, immediate-release, low-dose diclofenac potassium, developed for OTC use, offers a flexible daily dosing regimen with an initial dose of two tablets (2 x 12.5mg) followed by one or two tablets up to a maximum daily dose of six tablets (75 mg/day). The maximum plasma drug concentration is reached 30 minutes after administration, and the mean terminal half-life is 1-2 hours, allowing a 4- to 6-hour duration of activity, depending on the condition. Thirteen randomised, double-blind trials with both placebo and active controls have demonstrated the efficacy of diclofenac potassium 12.5mg tablets in conditions suitable for treatment with OTC medication, for example, acute lower back pain, headache, acute pain after dental extraction, symptoms of cold and influenza (including fever), and dysmenorrhoea. A single dose of diclofenac potassium 12.5mg is the lowest recommended effective dose. A two-tablet single dose of 25mg is at least as effective as ibuprofen 400mg. A flexible dosing regimen of an initial two tablets followed by one or two tablets up to a total daily dose of 75 mg is as effective as ibuprofen used in comparable fashion up to a total daily dose of 1200 mg. The incidence of adverse events in patients taking single or multiple doses of diclofenac potassium is similar to that of ibuprofen and placebo. In a safety study conducted to compare diclofenac potassium with ibuprofen for up to 3 months in patients with osteoarthritis of the knee, no differences in the pattern of adverse events were noted. There was no evidence of either hepatic injury or cardiovascular safety-related issues at any time during the study. Patients are generally capable of taking diclofenac potassium appropriately. A maximum OTC treatment duration of 5 days for pain and 3 days for fever is recommended.


Using self-monitoring to detect and manage raised blood pressure and pre-eclampsia during pregnancy: the BUMP research programme and its impact.
Raised blood pressure affects around ten percent of pregnancies worldwide, causing maternal and perinatal morbidity and mortality. Self-monitoring of blood pressure during higher-risk or hypertensive pregnancy has been shown to be feasible, acceptable, safe, and no more expensive than usual care alone. Additionally, self-testing for proteinuria has been shown to be just as accurate as healthcare professional testing, creating the potential for monitoring of multiple indicators through pregnancy. The work suggests however, that an organisational shift is needed to properly use and see benefits from self-monitored readings. This paper describes the findings from a large programme of work examining the use of self-monitoring in pregnancy, summarising the findings in the context of the wider literature and current clinical context. The BUMP Research Programme developed and tested self-monitoring and self-testing interventions for pregnancy. The work showed that self-monitoring during pregnancy was feasible, acceptable, safe, and no more expensive, but did not improve the detection or control of hypertension.


Risk factors for tuberculosis among inmates: a retrospective analysis.
This paper examined risk factors associated with TB among inmates, over a 7-year period, and the association of ethnicity and gender with these risk factors. We performed retrospective analysis of data on former inmates from a county jail. TB status at admission was explained with demographics, behavioral risk factors, and incarceration factors. We examined ethnicity and gender defenses on the risk factors. A total of 441 TB cases and 478 non-TB cases were included. Inmates were more likely to have TB if they were whites, unmarried, homeless, alcohol abusers, and HIV positive. Inmates with TB had even lower socioeconomic status and more behavioral risk factors than other inmates. They had fewer incarcerations and less serious crimes, but longer jail stays. TB risk factors differed by ethnicity and gender. TB control in jails requires intervention in the communities where inmates live. Correctional health is a critical part of public health. Public health nurses are responsible for better understanding and improving health care for this high-risk and difficult-to-reach population.


Milk allergy/intolerance and atopic dermatitis in infancy and childhood.
Adverse reactions to cow's milk proteins are usually indicated as cow's milk allergy/intolerance (CMPA/CMPI) because no differentiation is possible on the basis of symptoms, and there is no reliable single laboratory test available for the diagnosis of CMPA or CMPI. Elimination and challenge tests for cow's milk proteins using strict, well-defined diagnostic criteria are required for the diagnosis of CMPA/CMPI. Atopic dermatitis (AD) is one of the most common symptoms of CMPA/CMPI. Approximately one third of AD children have a diagnosis of CMPA/CMPI according to elimination diet and challenge tests, and about 40-50% of children < 1 year of age with CMPA/CMPI have AD. Many children with AD and CMPA/CMPI develop a complete tolerance to CMP in a few years. Children with persisting forms of CMPA/CMPI have a more frequent history of familial atopic disease, change in CMPA/CMPI manifestations over time and very high frequency of multiple food intolerance and allergic diseases. Many children who outgrow their AD develop other allergic diseases, such as rhinitis or asthma. The simultaneous development of allergic tolerance in one organ and the intolerance or atopic disease in another organ suggest that genetic, immunologic and environmental factors play a complex role in the natural history of AD and other atopic diseases.


The double hatchet flap: a workhorse in head and neck local flap reconstruction.
A double triangular flap, or hatchet flap, with a partial cutaneous pedicle, has great versatility for facial reconstruction, yet there has been little published discussion regarding the potential applications and/or modifications of the flap. A total of 483 cutaneous malignant neoplasms have been excised and repaired by the senior author (C.C.M.) using a modified bilateral hatchet flap; 366 of the neoplasms were located in the head and neck region. The flap has been used to reconstruct defects in the scalp, eyebrow, lower eyelid, nasal tip, cheek, chin, arms, and torso, with no cases of flap loss. The design of the flap and our modification will be discussed in detail, along with a description of 4 representative cases.


Cine MR in the evaluation of normal and abnormal CSF flow: intracranial and intraspinal studies.
Evaluation of intracranial and intraspinal CSF flow was accomplished by the use of cardiac gated gradient echo magnetic resonance (MR) technique. Normal patterns of pulsatile flow within the ventricles, cisterns and cervical subarachnoid space were established by this technique and these observations were compared to prior description of CSF flow. With systole there is downward (caudal) flow of CSF in the aqueduct of Sylvius, the foramen of Magendie, the basal cisterns and the dorsal and ventral subarachnoid spaces while during diastole, upward (cranial) flow of CSF in these same structures is seen. The relationships between the cardiac cycle and the CSF pulsations are demonstrated on both magnitude reconstruction and phase reconstruction MR images. Calculations of actual fluid velocity within CSF containing spaces can be obtained from the phase reconstruction images and holds promise for a more accurate analysis of CSF flow. In conditions which result in alterations of flow, cine MR dramatically shows either obstruction or excessively turbulent flow within the CSF pathways. The site of obstructed flow whether in the third ventricle, aqueduct, fourth ventricle, or subarachnoid space can be appreciated by changes in or absence of the normal hypointense signal. Cystic cord lesions such as congenital syringohydromyelia and posttraumatic spinal cord cysts may show pulsatile flow of CSF, a fact which can relate to progressive enlargement of these cysts. The distinction between myelomalacia and cyst formation in the cord is facilitated by the technique. Although the use of cine MR for the analysis of CSF flow is in its infancy, our experience indicates that this technique is useful in a wide range of pathological conditions including, but not limited to, conditions resulting in hydrocephalus or cystic cord lesions.


Terra firma-forme dermatosis.
Terra firma-forme dermatosis (TFFD) is an uncommon disorder of keratinization with an unknown etiology in which patients present with dirt-like lesions that are resistant to washing. A 6-year old girl presented with the complaint of an asymptomatic brownish black dirt-like eruption on her body. Her parents reported no response to washing with soap and water. Dermatologic examination revealed brown hyperpigmented patches on the trunk and abdominal region. TFFD was suspected, and isopropyl alcohol was applied to the patient's lesions. All lesions completely disappeared after rubbing with alcohol. Terra firma-forme dermatosis is a relatively recently described entity that is much more common than might be expected when surveying the medical literature. With the very few reports found in the literature about TFFD, we believe that an increased awareness of this entity among primary care physicians would help decrease unnecessary worries or medical procedures, since TFFD lesions simply resolve by rubbing with isopropyl alcohol.


A comparison of abstract rules in the prefrontal cortex, premotor cortex, inferior temporal cortex, and striatum.
The ability to use abstract rules or principles allows behavior to generalize from specific circumstances. We have previously shown that such rules are encoded in the lateral prefrontal cortex (PFC) and premotor cortex (PMC). Here, we extend these investigations to two other areas directly connected with the PFC and the PMC, the inferior temporal cortex (ITC) and the dorsal striatum (STR). Monkeys were trained to use two abstract rules: "same" or "different". They had to either hold or release a lever, depending on whether two successively presented pictures were the same or different, and depending on which rule was in effect. The rules and the behavioral responses were reflected most strongly and, on average, tended to be earlier in the PMC followed by the PFC and then the STR; few neurons in the ITC reflected the rules or the actions. By contrast, perceptual information (the identity of the pictures used as sample and test stimuli) was encoded more strongly and earlier in the ITC, followed by the PFC; they had weak, if any, effects on neural activity in the PMC and STR. These findings are discussed in the context of the anatomy and posited functions of these areas.


Evaluating the articulation index for auditory-visual consonant recognition.
Adequacy of the ANSI standard for calculating the articulation index (AI) [ANSI S3.5-1969 (R1986)] was evaluated by measuring auditory (A), visual (V), and auditory-visual (AV) consonant recognition under a variety of bandpass-filtered speech conditions. Contrary to ANSI predictions, filter conditions having the same auditory AI did not necessarily result in the same auditory-visual AI. Low-frequency bands of speech tended to provide more benefit to AV consonant recognition than high-frequency bands. Analyses of the auditory error patterns produced by the different filter conditions showed a strong negative correlation between the degree of A and V redundancy and the amount of benefit obtained when A and V cues were combined. These data indicate that the ANSI auditory-visual AI procedure is inadequate for predicting AV consonant recognition performance under conditions of severe spectral shaping.


Prognostic significance of TERT promoter and BRAF mutations in TIR-4 and TIR-5 thyroid cytology.
Follicular-derived thyroid cancers generally have a good prognosis, but in a minority of cases, they have an aggressive behavior and develop distant metastases, with an increase in the associated mortality. None of the prognostic markers currently available prior to surgery can identify such cases. TERT promoter and BRAF gene mutations were examined in a series of 436 consecutive TIR-4 and TIR-5 nodes referred for surgery. Follow-up (median: 59 months, range: 7-293 months) was available for 384/423 patients with malignant nodes. TERT promoter and BRAF mutations were detected in 20/436 (4.6%) and 257/434 thyroid nodules (59.2%), respectively. At the end of the follow-up, 318/384 patients (82.8%) had an excellent outcome, 48/384 (12.5%) had indeterminate response or biochemical persistence, 18/384 (4.7%) had a structural persistence or died from thyroid cancer. TERT promoter mutations correlated with older age (P < 0.0001), larger tumor size (P = 0.0002), oxyntic and aggressive PTC variants (P = 0.01), higher tumor stages (P < 0.0001), distant metastases (<0.0001) and disease outcome (P < 0.0001). At multivariate analysis, TERT promoter mutation was not an independent predictor of disease outcome. TERT promoter mutation- (OR: 40.58; 95% CI: 3.06-539.04), and N1b lymph node metastases (OR: 40.16, 95% CI: 3.48-463.04) were independent predictors of distant metastases. BRAF mutation did not predict the outcome, and it correlated with a lower incidence of distant metastases (P = 0.0201). TERT promoter mutation proved an independent predictor of distant metastases, giving clinicians the chance to identify many of the patients who warranted more aggressive initial treatment and closer follow-up.


State-based and demographic variation in parent-reported medication rates for attention-deficit/hyperactivity disorder, 2007-2008.
Medication is the most effective treatment of attention-deficit/hyperactivity disorder (ADHD), a common neurobehavioral disorder of childhood. We used data from the 2007-2008 National Survey of Children's Health to calculate weighted estimates of parent-reported ADHD and medication treatment among US children aged 4 to 17 years, by state and sex-stratified age. State-based rates of ADHD medication treatment ranged from 33% in Nevada to 79% in Mississippi; rates of medicated ADHD were higher among boys than girls at every age. State-based investigations of ADHD medication treatment factors are needed, and our findings may inform these public health efforts.


Prognostic value of cytokeratin 19 fragment (CYFRA 21-1) and cytokeratin-positive cells in bone marrow samples of breast cancer patients.
The aim of this study was to investigate the relationship between the detection of micrometastatic cells by immunocytochemistry (ICC) with an anticytokeratin antibody and cytokeratin fragment (CYFRA 21-1) expression detected by an immunofluorescent assay in bone marrow of breast cancer patients. Micrometastatic CK+ cells were screened with a pancytokeratin antibody A45 B/B3 from bone marrow aspiration samples of 102 breast cancer patients (65 primary tumors, 10 local recurrences and 27 distant metastases). CYFRA 21-1 levels were assessed in bone marrow supernatant of these patients before collection of the mononucleated interface cells on a Ficoll-Hypaque density gradient and in 20 control patients. CYFRA 21-1 and CK+ cell detection by ICC were both correlated with clinical stage. CYFRA 21-1 was significantly elevated in patients with micrometastatic disease detected by ICC: 4.77 ng/mL (+/- 10.87 SD) versus 1.00 ng/mL (+/-1.36 SD) in patients with negative ICC (p=0.01). In univariate analysis, a CYFRA 21-1 value > or =1 ng/mL and the presence of CK+ cells were associated with a poorer survival for patients with stage I to III breast cancer (n=65). On multivariate analysis, only pathological nodal status and presence of CK+ cells in bone marrow were independent prognostic factors for overall survival. In conclusion, in this series CYFRA 21-1 was correlated with detection of CK+ cells by ICC in bone marrow, but cannot replace ICC. The presence of CK+ cells in bone marrow remains a strong independent prognostic factor in primary breast cancer.


Combining Ketamine, Brain Stimulation (rTMS) and Mindfulness Therapy (TIMBER) for Opioid Addiction.
Opioid addiction in the United States currently presents a national crisis despite availability of different treatments. Prior findings suggest that both repetitive transcranial magnetic stimulation (rTMS) and subanesthetic dose of ketamine are efficacious in patients with opioid use disorders (OUD) when administered in isolation. However, their therapeutic value may be undermined by varying clinical responses that tend to dissipate with treatment cessation. There has been no study to date that has used a combination of both for OUD, and there are still many unanswered questions with respect to both. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation of memories) therapy attempts to alter the expression of emotionally charged memories such as traumatic memories, and has been successfully tried in chronic post-traumatic stress disorder (PTSD) and in combination with memory-altering pharmacotherapy like ketamine infusion. By a combination of extinction and reconsolidation of memory approaches, TIMBER works to not over-flood and/or retraumatize as is seen in other treatment approaches. TIMBER involves a balanced combination of both the memory extinction and memory reconsolidation approaches (rather than extinction-only approaches) which explains its superior efficacy in PTSD and benefit in substance use disorders.


Microglia specific fluorescent probes for live cell imaging.
Small molecule fluorescent probes offer significant advantages over conventional antibody and fluorescent protein labeling techniques. Here we present and , dyes that label live microglia specifically. They may be applied to the isolation and imaging of live microglia when investigating their role in neuroinflammatory diseases.


Electron transfer between horse ferritin and ferrihaemoproteins.
Reactions of reduced horse spleen ferritin with horse and Saccharomyces cerevisiae ferricytochromes c, cow ferricytochrome b5, sperm-whale metmyoglobin and Pseudomonas aeruginosa ferricytochrome c-551 were investigated by u.v.-visible spectrophotometry. In all cases the reduced ferritin reduced the ferrihaemoproteins. The rate of reduction varied from less than 0.2 M-1.s-1 for metmyoglobin to 1.1 x 10(3) M-1.s-1 for horse ferricytochrome c (0.1 M-phosphate buffer, pH 7.4, at 25 degrees C). We conclude that the mechanism of ferrihaemoprotein reduction involves long-range electron transfer through the coat of ferritin and that such electron transfer is rapid enough to account for the rates of iron release observed by other workers in reductive release assays.


Muscle stiffness and strength and their relation to hand function in children with hemiplegic cerebral palsy.
This study compared the passive stiffness of wrist flexors and the strength of wrist flexors and extensors in three different wrist positions (30 degrees of flexion, neutral, and 30 degrees of extension) between children with cerebral palsy (CP) and typically developing (TD) comparison children. It also examined associations between these characteristics and manual function in children with CP. Eleven children with spastic hemiplegic CP (six females, five males; mean age 8y 5mo [SD 1y 8mo], range 6-11y) and 11 TD children, matched for age and sex, took part in this study. Passive stiffness of muscles was measured as the torque/angle relation during passive motion. Isometric strength tests were performed and the time needed to complete three tasks based on the Jebsen-Taylor Hand Function Test was recorded. Flexor stiffness was higher in the group with CP. Strength of flexors and extensors in the group with CP was lower with the wrist extended. No difference among test positions was found in the TD group. Moderate correlations were observed between manual function and variables related to strength and stiffness of wrist muscles in the group with CP. Children with CP showed muscle alterations coherent with the use of the wrist in flexion. Intervention on these characteristics could have a positive impact on manual function.


Synthesis and antimicrobial activity of ZnTi-layered double hydroxide nanosheets.
Narrow size dispersion ZnTi-layered double hydroxide (LDH) nanosheets with lateral dimensions in the range 40-80 nm have been synthesised using a reverse microemulsion method. Electron Spin Resonance (ESR) and X-ray photoelectron spectroscopy (XPS) measurements reveal that Ti3+ sites are generated within these nanosized LDH platelets. The data show that the concentration of Ti3+ cations in the nanoplatelets is size-dependent, the 40 nm nanoplatelets have a bandgap of ca. 2.3 eV. The combination of photochemcially activity and nanoparticle size results in materials that exhibit high antipathogen activity under visible light. The biocidal efficacies of the LDHs have been investigated under visible light. The ZnTi-LDHs display size-dependent cytotoxicity against S. cerevisiae, S. aureus and E. coli in culture. The 40 nm ZnTi-LDH nanoplatelets (ZnTi-LDH-RM1) are the most potent resulting in 95% cell death. These nanoplatelets are more active compared to a conventionally prepared ZnTi-LDH or the nanoparticulate metal oxides WO3 and TiO2 (P25). The nanosized ZnTi-LDHs severely inhibit the growth of S. cerevisiae, S. aureus and E. coli in culture.


Post-renal transplant compliance.
A selective review was undertaken to identify factors which may affect a child's compliance with immunosuppressive therapies, post-renal transplant. Studies were categorised as either examining compliance from an experiential or selective attribution approach. There are multiple reasons for non-compliance. Children and families require much more support than previously recognised.


[Nature of intercellular interactions at various stages of post-transplantation immunity].
The paper presents the results of studies on the nature and frequency of intercellular interactions at various stages of posttransplantation immunity done by means of the grating microscope. The study was carried out in inbred mice. The donors of the skin included CBA mice (for the syngeneic system) and BALB/c mice (for the allogeneic system), and the recipients were CBA mice. The target cells were epidermal cells of the tails of mice of the appropriate lines. The interaction of the target cells with lymphocytes, thymocytes and macrophages obtained from the animals sensitized with the appropriate transplant were examined at various intervals after transplantation. The frequency and the nature of intercellular contacts were found to vary in relation to the time after grafting and the species of the graft. Numerous arches, bridges, outgrowths and microvilli were formed both between killer cells and immunocompetent cells and between lymphoid and non-lymphoid cells.


Multiple mechanisms determine the sensitivity of human-induced pluripotent stem cells to the inducible caspase-9 safety switch.
Expression of the inducible caspase-9 (iC9) suicide gene is one of the most appealing safety strategies for cell therapy and has been applied for human-induced pluripotent stem cells (hiPSC) to control the cell fate of hiPSC. iC9 can induce cell death of over 99% of iC9-transduced hiPSC (iC9-hiPSC) in less than 24 hours after exposure to chemical inducer of dimerization (CID). There is, however, a small number of resistant cells that subsequently outgrows. To ensure greater uniformity of the hiPSC response to iC9 activation, we purified a resistant population by culturing iC9-hiPSC with CID and analyzing the mechanisms by which the cells evade killing. We found that iC9-resistant hiPSC have significant heterogeneity in terms of their escape mechanisms from caspase-dependent apoptosis including reduced expression of iC9 by promoter silencing and overexpression of BCL2. As a consequence, modifying a single element alone will be insufficient to ensure sustained susceptibility of iC9 in all cells and prevent the eventual outgrowth of a resistant population. To solve this issue, we propose to isolate an iC9-sensitive population and show that this hiPSC line has sustained a uniform responsiveness to iC9-mediated growth control.


Co-occurrence of psychiatric and medical morbidity in primary care.
This study examines the co-occurrence of psychiatric and medical morbidity in primary care patients utilizing a health care clinic in Marshfield, Wisconsin. Previous research has shown that individuals with psychiatric disorders have higher rates of medical illness than people without psychiatric illness, but most prior studies have tended to confound the measures of psychiatric and medical morbidity. In addition, appropriate controls for bias resulting from different medical utilization patterns have sometimes been absent. The present study reports the medical diagnoses of persons who had been assessed for psychiatric disorder with a standardized psychiatric interview using research diagnostic criteria independent of their medical assessment. Psychiatric diagnoses are analyzed in relation to medical diagnoses at the time of the interview and for a one-year period--six months before and six months after that date. The results indicate that persons with mental disorder diagnoses have significantly more morbidity for the one-year study period. Although considerable congruence exists in the physical diagnoses recorded for both groups, those with mental disorders are more likely to have diagnoses of the digestive and genitourinary systems. Some sex differences are also explored.


Quantitation of differential renal function with Tc-99m MDP.
This study was designed to evaluate the usefulness of the bone tracer Tc-99m MDP for quantitative assessment of relative renal function as compared with renal imaging radiotracers used for that purpose. Differential renal function, i.e., the percent contribution each kidney makes to global renal function, was determined prospectively in 15 consecutive patients using Tc-99m MDP and a renal radionuclide tracer, either Tc-99m DTPA or Tc-99m GHA. Differential function was computed in all cases from the early (1-3 minutes) renal uptake of the tracers by region-of-interest analysis of the computer-acquired data. There was a high correlation between values of differential function obtained with Tc-99m MDP and those obtained with Tc-99m DTPA or Tc-99m GHA (r = 0.98, P less than 0.0001). Qualitative assessment of the images revealed equivalent scintigraphic patterns in all patients. It is concluded that the early characteristics of renal handling of Tc-MDP are sufficiently similar to those of Tc-DTPA and Tc-GHA so that accurate estimates of differential renal function are possible with this agent, and that Tc-MDP-determined renal differential most likely reflects differential glomerular filtration rate.


A parallel algorithm for step- and chain-growth polymerization in molecular dynamics.
Classical Molecular Dynamics (MD) simulations provide insight into the properties of many soft-matter systems. In some situations, it is interesting to model the creation of chemical bonds, a process that is not part of the MD framework. In this context, we propose a parallel algorithm for step- and chain-growth polymerization that is based on a generic reaction scheme, works at a given intrinsic rate and produces continuous trajectories. We present an implementation in the ESPResSo++ simulation software and compare it with the corresponding feature in LAMMPS. For chain growth, our results are compared to the existing simulation literature. For step growth, a rate equation is proposed for the evolution of the crosslinker population that compares well to the simulations for low crosslinker functionality or for short times.


Fasting insulin serum levels and psychopathology profiles in male schizophrenic inpatients treated with olanzapine or risperidone.
Recent studies have suggested that higher insulin levels are associated with better psychopathology profiles in cross-sectional samples of patients with schizophrenia. This study examines whether drug-induced fasting insulin changes between third and eight week of treatment are related to clinical improvement in non-diabetic patients receiving the atypical neuroleptics: risperidone or olanzapine. non-diabetic men with a diagnosis of schizophrenia according to the DSM-IV diagnostic classification were recruited from psychiatric inpatient units. Following a drug-free period, neuroleptic treatment was initiated (risperidone n=36, olanzapine n=35) and doses were adjusted to achieve maximal clinical efficacy. All patients were hospitalized throughout the study. Initial and final evaluations of serum insulin levels and psychopathology (assessed with the Positive and Negative Syndrome Scale, PANSS), were carried out at weeks 3 and 8 after the onset of treatment, respectively. There were no differences between and within the risperidone and olanzapine groups in changes of serum insulin level between the third and eighth week of treatment. In the olanzapine group, Pearson correlation analysis revealed a significant negative correlation between changes in fasting serum insulin levels and the PANSS-Total, Positive and General Psychopathology subscale scores. Only improvement in the PANSS-Negative Symptom subscale score was not correlated with insulin level change between the third and eighth week of treatment. In the risperidone group, correlations between PANSS subscales scores and the corresponding serum insulin levels change were positive, albeit statistically non-significant. In both groups the improvement in PANSS-Total scores was not correlated with changes in BMI. Olanzapine-related changes in endogenous fasting insulin levels were correlated with clinical improvement in acutely ill non-diabetic schizophrenic patients. Because the interesting linkage between insulin and positive and negative symptoms could be an epiphenomenon, randomized studies are needed to further explore the role of insulin in therapeutic responses in patients with schizophrenia.


Magnetic microrods as a tool for microrheology.
Dynamics of superparamagnetic rods in crossed constant and alternating magnetic fields as a function of field frequency are studied and it is shown that above the critical value of the amplitude of the alternating field the rod oscillates around the direction of the alternating field. The fit of the experimentally measured time dependence of the mean orientation angle of the rod allows one to determine the ratio of magnetic and viscous torques which act on the rod. The protocol of microrheological measurements consists of recording the dynamics of the orientation of the rod when the magnetic field is applied at an angle to the rod and observing its relaxation due to the accumulated elastic energy after the field is switched off. The microrheological data obtained are in reasonable agreement with the macrorheological measurements.